Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the NAD dependent oxidation of IMP to xanthosine monophosphate (XMP), the committed step in guanosine monophosphate biosynthesis. We have determined the crystal structures of IMPDH from T. foetus in the apo form at 2.3 E resolution and the enzyme-XMP complex at 2.6 E resolution. While the electron density for XMP in the complex structure is well-defined, the NAD+ binding site and a nearby loop containing the catalytic cysteine (Cys-319) are disordered. This disorder at the active site suggests that a high degree of flexibility may be inherent to the catalytic function of IMPDH, making this area a difficult target for structure-based inhibitor design. We have recently co-crystallized T. foetus IMPDH with NAD+ and have collected data to 3.5 E resolution on our R-axis IV. We hope to obtain data to 2.5 E at SSRL. The NAD+ may help to stabilize these sites, facilitating the structure based design of inhibitors.